This research proposal will continue to focus on a systematic study of the physiological and physiopathological relationships between the two major endocrine systems that control adrenal and gonadal function. The project will study the role of the hypothalamic-pituitary-adrenal axis and of the hypothalamic neuropeptides that control it in the physiology of the menstrual cycle and in the etiology of the hypothalamic amenorrhea or anovulatory syndrome. The studies will be performed in the female rhesus monkey, an animal model chosen specifically for its similarity with the human in terms of the menstrual cycle and reproductive function. Presently, we have demonstrated a direct causal inhibitory action of CRH, the principal neuropeptide in control of adrenal function, on LH and FSH secretion in the ovariectomized (OVX) monkey.
In aim 1, we will investigate whether other neuropeptides which are released within the hypothalamus by stress or immune challenge, for ex. vasopressin, also exert such an inhibitory influence on gonadotropin release in the OVX monkey.
In aim 2, we will study whether and how ovarian steroid replacement therapy in the OVX monkey modulate these adrenal-gonadal axes relationships. Such ovarian steroid modulation, of course, would bear major consequences in regard to the physiopathological relationships between these two endocrine axes during the normal menstrual cycle, as studied in aim 3. The objective of this aim in the intact animal will be to determine both how the adrenal axis, in a """"""""permissive"""""""" role may promote specific events so that the ovulatory cycle is facilitated, and how subtle abnormalities of the hypothalamopituitary-adrenal axis can """"""""inhibit"""""""" or interfere with the normal sequence of events that characterize the ovulatory menstrual cycle.
Aim 4 will study the role of adrenal axis neuropeptides in the pathology of the menstrual cycle, as exemplified in the hypothalamic amenorrhea syndrome. Overall, these studies will shed light on the processes whereby activation of the adrenal axis, such as that which occurs in 'stress', interferes with normal reproductive function and on the mechanisms whereby the adrenal axis may act in support of normal cyclic function.
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